Review
Immunology
Christophe Macri, Devi Jenika, Cassandra Ouslinis, Justine D. Mintern
Summary: Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in adaptive immunity. Targeting antigen directly to DCs is a selective vaccination strategy that takes advantage of the antigen uptake and presentation functions of DC subsets. This review focuses on DC-targeted vaccination strategies aimed at inducing effective cross-presentation for CD8+ T cell immunity. Receptors highly expressed by mouse and human cDCs, such as DEC205, Clec9A, and XCR1, are explored. The outcomes of DC-targeted vaccination in mouse models and human clinical trials are discussed, highlighting its potential for the prevention and treatment of tumors and infectious diseases.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Inga Peciuliene, Egle Jakubauskiene, Laurynas Vilys, Ruta Zinkeviciute, Kotryna Kvedaraviciute, Arvydas Kanopka
Summary: This article investigates the effects of short-term hypoxia on gene splicing and protein expression. The study found that the splicing of genes associated with cellular stress changes under short-term hypoxic conditions, but differs from that under prolonged hypoxia. Additionally, short-term cellular hypoxia increases protein phosphatase expression, which is important for altering gene splicing.
Review
Immunology
Ray A. Ohara, Kenneth M. Murphy
Summary: Cross-priming, initially recognized in cytotoxic T lymphocyte (CTL) responses, involves the presentation of minor histocompatibility antigens by antigen presenting cells (APCs) derived from immunizing cells. As understanding of T cell receptor antigen recognition progressed, cross-priming was redefined as cross-presentation and expanded to include different forms of antigens and APCs not involved in in vivo CTL priming. In vitro cell models have been utilized for studying cross-presentation, but recent studies have shown differences between these models and in vivo APCs. Current research focuses on validating in vivo pathways and gene candidates for cross-presentation, and evaluating their contributions to CTL responses across different antigens and immunologic settings.
SEMINARS IN IMMUNOLOGY
(2023)
Review
Immunology
Francois-Xavier Mauvais, Peter van Endert
Summary: The critical role of conventional dendritic cells in the immune response to tumors and pathogens is well-established. However, various other cell types, including myeloid, lymphoid, endothelial, epithelial, and stromal cells, have been shown to also possess the ability to cross-present antigens. This review analyzes the literature on this topic, discussing the antigens and readouts used, mechanistic insights, and in vivo experimentation. While many studies rely on artificial systems, there is evidence to suggest that cross-presentation by non-dendritic cells may have significant implications in anti-tumor immunity and autoimmunity.
SEMINARS IN IMMUNOLOGY
(2023)
Review
Medicine, Research & Experimental
Tingting Zhang, Adila Aipire, Yijie Li, Changying Guo, Jinyao Li
Summary: This review summarizes the mechanisms of cross-presentation (XPT) and its application in tumor immunotherapy. Dendritic cells enhance their antigen presentation capacity through receptor-mediated internalization of exogenous antigens, endosome escape, engagement of other XPT-related proteins, and the use of adjuvants, thereby improving the outcomes of DC-based therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Immunology
Takumi Kawasaki, Moe Ikegawa, Taro Kawai
Summary: The lungs have an immune defense mechanism that uses various cells to eliminate harmful pathogens and activate T cell immune response. In addition to immune cells, other lung cells also participate in antigen presentation and T cell activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Nataschja I. Ho, Marcel G. Camps, Juan J. Garcia-Vallejo, Erik Bos, Abraham J. Koster, Martijn Verdoes, Yvette van Kooyk, Ferry Ossendorp
Summary: Dendritic cells have the unique ability to present exogenous antigens through MHC class I molecules, with the antigen being conserved in storage compartments for days. These compartments in DCs lack certain molecules involved in MHC class I processing, and the co-localization of active cathepsin X with protein antigen suggests a novel role for cathepsin X in antigen processing and cross-presentation. These compartments can preserve protein antigens from different uptake routes and contribute to long-lasting antigen cross-presentation.
Article
Immunology
Gerardo Suarez-Rojas, Jose C. Crispin
Summary: This review summarizes the kinase and phosphatase defects in T cells from patients with SLE and discusses their significance for disease development and expression.
CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Gaetan Barbet, Priyanka Nair-Gupta, Michael Schotsaert, Stephen T. Yeung, Julien Moretti, Fabian Seyffer, Giorgi Metreveli, Thomas Gardner, Angela Choi, Domenico Tortorella, Robert Tampe, Kamal M. Khanna, Adolfo Garcia-Sastre, J. Magarian Blander
Summary: The study explains how viruses target host cell antigen-processing pathways, focusing on MHC-I molecules and the re-routing of ERGIC-resident MHC molecules to phagosomal vesicles for cross-presentation. It suggests that even without TAP, protective CD8(+) T cells can still be mobilized during viral infection, highlighting a noncanonical cross-presentation pathway.
Article
Oncology
Tim B. Fessenden, Lauren E. Stopfer, Fiona Chatterjee, Julian Zulueta, Josh Mesfin, Therese Cordero Dumit, Irene Reijers, Esmee P. Hoefsmit, Christian Blank, Forest White, Stefani Spranger
Summary: Cytotoxic CD8(+) T cells must recognize tumor-derived antigens to achieve effective tumor elimination. Our study shows that dendritic cells induce cytotoxic CD8(+) T-cell responses by cross-presenting tumor-derived peptides, and the proportion of membrane-derived neoantigens is associated with reduced survival and treatment response.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Allergy
Janice J. Huang, Samantha B. Gaines, Mateo L. Amezcua, Tamar R. Lubell, Peter S. Dayan, Marissa Dale, Alexis D. Boneparth, Mark D. Hicar, Robert Winchester, Mark Gorelik
Summary: This study aimed to analyze the immunologic features of MIS-C patients compared to febrile controls. The results showed that elevated cytokines, activation of type 1 dendritic cells, and dysregulation of NK cells were key features in the pathophysiology of this syndrome.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Hejin Jiang, Rui Liu, Lu Wang, Xinyue Wang, Mengmeng Zhang, Sisi Lin, Zhenping Cao, Feng Wu, Yingbin Liu, Jinyao Liu
Summary: Chirality plays a critical role in biological systems, and this study demonstrates the potential of using supramolecular chiral polymer micelles (SCPMs) to activate the immune system for disease prevention and treatment.
ADVANCED MATERIALS
(2023)
Review
Biochemistry & Molecular Biology
Alice Coillard, Elodie Segura
Summary: This study reviews the research on mouse mo-DC, evaluates the in vivo evidence for monocyte-derived antigen-presenting cells, and proposes that mo-DC may present antigens to effector T cells locally in tissues, playing a complementary role to cDCs.
MOLECULAR IMMUNOLOGY
(2021)
Article
Engineering, Biomedical
Yingying Shi, Chunqi Zhu, Yu Liu, Yichao Lu, Xiang Li, Bing Qin, Zhenyu Luo, Lihua Luo, Mengshi Jiang, Junlei Zhang, Guannan Guan, Cheng Zheng, Jian You
Summary: A study has identified a novel vaccine carrier that enhances the activation and maturation of dendritic cells, leading to a stronger cytotoxic T lymphocyte response and improved host defense against cancer or infection. The findings shed new light on the design and optimization of vaccines for currently intractable diseases.
ADVANCED HEALTHCARE MATERIALS
(2021)
Review
Oncology
Jaime Gonzalez-Montero, Carlos I. Rojas, Mauricio Burotto
Summary: MAP4K4 is a serine/threonine kinase that plays a critical role in embryogenesis, cellular migration, and the development of metabolic diseases and cancer. Inhibiting MAP4K4 function has been shown to reduce tumor proliferation, migration, and invasion, making it a potential therapeutic target for various types of cancer. Specific MAP4K4 inhibitors have been developed but have not yet been tested in cancer patients.
FRONTIERS IN ONCOLOGY
(2023)
Article
Immunology
Henrique G. Colaco, Andre Barros, Ana Neves-Costa, Elsa Seixas, Dora Pedroso, Tiago Velho, Katharina L. Willmann, Pedro Faisca, Gerlinde Grabmann, Hyon-Seung Yi, Minho Shong, Vladimir Benes, Sebastian Weis, Thomas Koecher, Luis F. Moita
Summary: Tetracycline antibiotics targeting the mitoribosome were found to protect against sepsis by perturbing the electron transport chain and reducing tissue damage in the lung, while increasing fatty acid oxidation and glucocorticoid sensitivity in the liver. This study demonstrates that mitochondrial protein synthesis inhibition leading to ETC perturbation is a mechanism for inducing disease tolerance beyond the antibacterial activity of these antibiotics.
Article
Immunology
Luis Almeida, Ayesha Dhillon-LaBrooy, Carla N. Castro, Nigatu Adossa, Guilhermina M. Carriche, Melanie Guderian, Saskia Lippens, Sven Dennerlein, Christina Hesse, Bart N. Lambrecht, Luciana Berod, Leif Schauser, Bruce R. Blazar, Markus Kalesse, Rolf Mueller, Luis F. Moita, Tim Sparwasser
Summary: Linezolid and other ribosomal-targeting antibiotics effectively inhibit T cell activity, disrupt mitochondrial function, reduce oxidative phosphorylation levels, and prevent the occurrence of autoimmune diseases.
Article
Cell Biology
Jolien Vandewalle, Steven Timmermans, Ville Paakinaho, Lies Vancraeynest, Liza Dewyse, Tineke Vanderhaeghen, Charlotte Wallaeys, Lise Van Wyngene, Kelly Van Looveren, Louise Nuyttens, Melanie Eggermont, Sylviane Dewaele, Tiago R. Velho, Luis F. Moita, Sebastian Weis, Christoph Sponholz, Leo A. van Grunsven, Mieke Dewerchin, Peter Carmeliet, Karolien De Bosscher, Johan Van de Voorde, Jorma J. Palvimo, Claude Libert
Summary: Defects in the glucocorticoid receptor signaling pathway exacerbate sepsis pathophysiology by reducing lactate clearance and sensitizing mice to lactate-induced toxicity, ultimately leading to lethal vascular collapse.
Article
Multidisciplinary Sciences
Irene Cimino, Hanna Kim, Y. C. Loraine Tung, Kent Pedersen, Debra Rimmington, John A. Tadross, Sara N. Kohnke, Ana Neves-Costa, Andre Barros, Stephanie Joaquim, Don Bennett, Audrey Melvin, Samuel M. Lockhart, Anthony J. Rostron, Jonathan Scott, Hui Liu, Keith Burling, Peter Barker, Menna R. Clatworthy, E-Chiang Lee, A. John Simpson, Giles S. H. Yeo, Luis F. Moita, Kendra K. Bence, Sebastian Beck Jorgensen, Anthony P. Coll, Danna M. Breen, Stephen O'Rahilly
Summary: GDF15 plays a crucial role in activating the hypothalamic-pituitary-adrenal (HPA) axis; It is essential for the protective HPA response to toxins that do not induce a substantial cytokine response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Isabel Pereira-Castro, Beatriz C. Garcia, Ana Curinha, Ana Neves-Costa, Eduardo Conde-Sousa, Luis F. Moita, Alexandra Moreira
Summary: This study investigates the functional significance of alternative polyadenylation (APA) in the regulation of MCL1 in T cells. The results show that T cell activation leads to an increase in mRNA isoforms with short 3' UTRs resulting from APA, which in turn increases the expression of the shorter pA1 isoform and MCL1 protein levels. The less efficiently translated pA2 isoform is downregulated by miR-17. Depletion of either pA1 or pA2 isoforms causes defects in mitochondria morphology, increased apoptosis, and impaired cell proliferation. APA plays a key role in regulating MCL1 protein levels and is essential for T cell survival.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Editorial Material
Critical Care Medicine
Luis F. Moita, Timothy E. Sweeney, Pedro Povoa
INTENSIVE CARE MEDICINE
(2022)
Article
Multidisciplinary Sciences
Debanjan Mukherjee, Angelo Ferreira Chora, Jean-Christophe Lone, Ricardo S. Ramiro, Birte Blankenhaus, Karine Serre, Mario Ramirez, Isabel Gordo, Marc Veldhoen, Patrick Varga-Weisz, Maria M. Mota
Summary: This study reveals that the microbiota colonizing the lung can promote respiratory distress syndrome and mortality during malaria infections. Parasite sequestration in the lung results in sustained immune activation and production of anti-inflammatory cytokine compromises microbial control, leading to severe lung disease. Clearance of bacteria prevents MA-ARDS-associated lethality. Hence, the balance between the host's anti-inflammatory response and microbial control should be considered when intervening against respiratory complications.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Nuno Carvalho, Elisabete Carolino, Helder Coelho, Ana Coias, Madalena Trindade, Joao Vaz, Brigitta Cismasiu, Catarina Moita, Luis Moita, Paulo Matos Costa
Summary: Appendicitis is a common surgical emergency, and this study suggests that allergic responses, specifically the involvement of eosinophils and interleukin-5, play significant roles in its pathophysiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Amichay Afriat, Vanessa Zuzarte-Luis, Keren Bahar Halpern, Lisa Buchauer, Sofia Marques, Angelo Ferreira Chora, Aparajita Lahree, Ido Amit, Maria M. Mota, Shalev Itzkovitz
Summary: This study characterized the temporal expression programs of the rodent malaria parasite Plasmodium berghei ANKA and the host hepatocyte in a zonally controlled manner using single-cell RNA sequencing and single-molecule transcript imaging. The study identified differences in parasite gene expression in distinct zones and identified a subpopulation of hepatocytes with reduced levels of Plasmodium transcripts and parasitophorous vacuole breakdown. These findings provide insights into the liver stage of Plasmodium infection.
Article
Biology
Angelo Ferreira Chora, Dora Pedroso, Eleni Kyriakou, Nadja Pejanovic, Henrique Colaco, Raffaella Gozzelino, Andre Barros, Katharina Willmann, Tiago Velho, Catarina F. Moita, Isa Santos, Pedro Pereira, Silvia Carvalho, Filipa Batalha Martins, Joao A. Ferreira, Sergio Fernandes de Almeida, Vladimir Benes, Josef Anrather, Sebastian Weis, Miguel P. Soares, Arie Geerlof, Jacques Neefjes, Michael Sattler, Ana C. Messias, Ana Neves-Costa, Luis Ferreira Moita, Yousef Abu-Amer
Summary: Anthracyclines, a class of commonly used and effective anticancer drugs, were found to decrease the transcription of NF-kappa B-dependent gene targets and disturb the complexes formed between NF-kappa B subunit RelA and its DNA-binding sites. The anthracycline variants without inducing DNA damage also suppressed inflammation, which has implications for cancer therapy and the development of anti-inflammatory drugs with limited side effects.
Article
Immunology
Angelo Ferreira Chora, Sofia Marques, Joana Lisboa Goncalves, Priscila Lima, Daniel Gomes da Costa, Daniel Fernandez-Ruiz, Maria Ines Marreiros, Pedro Ruivo, Tania Carvalho, Ruy M. Ribeiro, Karine Serre, William R. Heath, Bruno Silva-Santos, Ann T. Tate, Maria M. Mota
Summary: During malaria infection, Plasmodium replicates in the liver and later infects red blood cells. It has been commonly believed that liver infection does not affect disease pathology as clinical manifestations only occur during the blood stage. However, a study using a mouse model uncoupling liver and blood stages of infection revealed that signals from both stages determine mortality outcomes. This finding was mediated by the activation of Vy4+ y8 T cells during the liver stage, which subsequently influenced cytokine profiles during the blood stage. The study also suggested that IL-17 produced by y8 T cells played a role in protecting mice from lethal cerebral malaria.
Meeting Abstract
Immunology
Katia Jesus, Andre Barros, Elsa Seixas, Luis Moita
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Meeting Abstract
Clinical Neurology
R. Oliveira, A. Neves-Costa, D. Pedroso, A. B. Barros, L. F. Moita, R. Gil-Gouveia
